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Aliases for VPS35 Gene

Aliases for VPS35 Gene

  • Vacuolar Protein Sorting 35 Homolog (S. Cerevisiae) 2 3
  • MEM3 3 4 6
  • Maternal-Embryonic 3 3 4
  • PARK17 3 6
  • HVPS35 3 4
  • Vacuolar Protein Sorting-Associated Protein 35 3
  • Vacuolar Protein Sorting 35 (Yeast Homolog) 2
  • Vacuolar Protein Sorting 35 (Yeast) 2
  • Vesicle Protein Sorting 35 4

External Ids for VPS35 Gene

Summaries for VPS35 Gene

Entrez Gene Summary for VPS35 Gene

  • This gene belongs to a group of vacuolar protein sorting (VPS) genes. The encoded protein is a component of a large multimeric complex, termed the retromer complex, involved in retrograde transport of proteins from endosomes to the trans-Golgi network. The close structural similarity between the yeast and human proteins that make up this complex suggests a similarity in function. Expression studies in yeast and mammalian cells indicate that this protein interacts directly with VPS35, which serves as the core of the retromer complex. [provided by RefSeq, Jul 2008]

GeneCards Summary for VPS35 Gene

VPS35 (Vacuolar Protein Sorting 35 Homolog (S. Cerevisiae)) is a Protein Coding gene. Diseases associated with VPS35 include parkinson disease 17 and insulin autoimmune syndrome. Among its related pathways are Signaling by GPCR and beta-catenin independent WNT signaling.

UniProtKB/Swiss-Prot for VPS35 Gene

  • Acts as component of the retromer cargo-selective complex (CSC). The CSC is believed to be the core functional component of retromer or respective retromer complex variants acting to prevent missorting of selected transmembrane cargo proteins into the lysosomal degradation pathway. The recruitment of the CSC to the endosomal membrane involves RAB7A and SNX3. The CSC seems to associate with the cytoplasmic domain of cargo proteins predominantly via VPS35; however, these interactions seem to be of low affinity and retromer SNX proteins may also contribute to cargo selectivity thus questioning the classical function of the CSC. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX3-retromer mediates the retrograde endosome-to-TGN transport of WLS distinct from the SNX-BAR retromer pathway. The SNX27-retromer is believed to be involved in endosome-to-plasma membrane trafficking and recycling of a broad spectrum of cargo proteins. The CSC seems to act as recruitment hub for other proteins, such as the WASH complex and TBC1D5 (Probable). Required for retrograde transport of lysosomal enzyme receptor IGF2R and SLC11A2. Required to regulate transcytosis of the polymeric immunoglobulin receptor (pIgR-pIgA) (PubMed:15078903, PubMed:15247922, PubMed:20164305). Required for endosomal localization of FAM21C (PubMed:22070227). Mediates the association of the CSC with the WASH complex via FAM21 (PubMed:22070227, PubMed:24980502, PubMed:24819384). Required for the endosomal localization of TBC1D5 (PubMed:20923837).

Gene Wiki entry for VPS35 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for VPS35 Gene

Genomics for VPS35 Gene

Genomic Location for VPS35 Gene

Start:
46,656,132 bp from pter
End:
46,689,518 bp from pter
Size:
33,387 bases
Orientation:
Minus strand

Genomic View for VPS35 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for VPS35 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for VPS35 Gene

Regulatory Elements for VPS35 Gene

Proteins for VPS35 Gene

  • Protein details for VPS35 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q96QK1-VPS35_HUMAN
    Recommended name:
    Vacuolar protein sorting-associated protein 35
    Protein Accession:
    Q96QK1
    Secondary Accessions:
    • Q561W2
    • Q9H016
    • Q9H096
    • Q9H4P3
    • Q9H8J0
    • Q9NRS7
    • Q9NVG2
    • Q9NX80
    • Q9NZK2

    Protein attributes for VPS35 Gene

    Size:
    796 amino acids
    Molecular mass:
    91707 Da
    Quaternary structure:
    • Component of the heterotrimeric retromer cargo-selective complex (CSC), also decribed as vacuolar protein sorting subcomplex (VPS), formed by VPS26 (VPS26A or VPS26B), VPS29 and VPS35 (PubMed:11102511). The CSC has a highly elongated structure with VPS26 and VPS29 binding independently at opposite distal ends of VPS35 as central platform (By similarity). The CSC is believed to associate with variable sorting nexins to form functionally distinct retromer complex variants. The originally described retromer complex (also called SNX-BAR retromer) is a pentamer containing the CSC and a heterodimeric membrane-deforming subcomplex formed between SNX1 or SNX2 and SNX5 or SNX6 (also called SNX-BAR subcomplex); the respective CSC and SNX-BAR subcomplexes associate with low affinity. The CSC associates with SNX3 to form a SNX3-retromer complex. The CSC associates with SNX27, the WASH complex and the SNX-BAR subcomplex to form the SNX27-retromer complex (Probable). Interacts with VPS26A, VPS26B, VPS29, SNX1, SNX2, IGF2R, SNX3, GOLPH3, LRRK2, SLC11A2, FAM21A, FAM21C, FKBP15, WASH1, RAB7A, SNX27, KIAA0196, EHD1 (PubMed:11102511, PubMed:15078903, PubMed:17868075PubMed:22070227, PubMed:19553991, PubMed:21725319, PubMed:22070227, PubMed:22513087, PubMed:23331060, PubMed:23563491, PubMed:23395371, PubMed:24344282, PubMed:24980502, PubMed:17891154, PubMed:19531583). Interacts with MAGEL2; leading to recruitment of the TRIM27:MAGEL2 E3 ubiquitin ligase complex retromer-containing endosomes (PubMed:23452853).
    SequenceCaution:
    • Sequence=AAG01989.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=BAA91137.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=BAB14626.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for VPS35 Gene

neXtProt entry for VPS35 Gene

Proteomics data for VPS35 Gene at MOPED

Post-translational modifications for VPS35 Gene

  • Modification sites at PhosphoSitePlus
  • Ubiquitination at Lys24 and Lys396

Other Protein References for VPS35 Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

No data available for DME Specific Peptides for VPS35 Gene

Domains for VPS35 Gene

Gene Families for VPS35 Gene

HGNC:
  • PARK :Parkinson disease

Protein Domains for VPS35 Gene

Suggested Antigen Peptide Sequences for VPS35 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q96QK1

UniProtKB/Swiss-Prot:

VPS35_HUMAN
Family:
  • Belongs to the VPS35 family.:
    • Q96QK1
genes like me logo Genes that share domains with VPS35: view

Function for VPS35 Gene

Molecular function for VPS35 Gene

UniProtKB/Swiss-Prot Function: Acts as component of the retromer cargo-selective complex (CSC). The CSC is believed to be the core functional component of retromer or respective retromer complex variants acting to prevent missorting of selected transmembrane cargo proteins into the lysosomal degradation pathway. The recruitment of the CSC to the endosomal membrane involves RAB7A and SNX3. The CSC seems to associate with the cytoplasmic domain of cargo proteins predominantly via VPS35; however, these interactions seem to be of low affinity and retromer SNX proteins may also contribute to cargo selectivity thus questioning the classical function of the CSC. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX3-retromer mediates the retrograde endosome-to-TGN transport of WLS distinct from the SNX-BAR retromer pathway. The SNX27-retromer is believed to be involved in endosome-to-plasma membrane trafficking and recycling of a broad spectrum of cargo proteins. The CSC seems to act as recruitment hub for other proteins, such as the WASH complex and TBC1D5 (Probable). Required for retrograde transport of lysosomal enzyme receptor IGF2R and SLC11A2. Required to regulate transcytosis of the polymeric immunoglobulin receptor (pIgR-pIgA) (PubMed:15078903, PubMed:15247922, PubMed:20164305). Required for endosomal localization of FAM21C (PubMed:22070227). Mediates the association of the CSC with the WASH complex via FAM21 (PubMed:22070227, PubMed:24980502, PubMed:24819384). Required for the endosomal localization of TBC1D5 (PubMed:20923837).

Gene Ontology (GO) - Molecular Function for VPS35 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005488 binding --
GO:0005515 protein binding IPI 11102511
GO:0008565 protein transporter activity IBA --
genes like me logo Genes that share ontologies with VPS35: view

Phenotypes for VPS35 Gene

genes like me logo Genes that share phenotypes with VPS35: view

No data available for Enzyme Numbers (IUBMB) , Animal Models , Transcription Factor Targeting and HOMER Transcription for VPS35 Gene

Localization for VPS35 Gene

Subcellular locations from UniProtKB/Swiss-Prot for VPS35 Gene

Cytoplasm. Membrane; Peripheral membrane protein. Endosome. Early endosome. Late endosome. Note=Localizes to tubular profiles adjacent to endosomes. {ECO:0000269 PubMed:15078903}.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for VPS35 Gene COMPARTMENTS Subcellular localization image for VPS35 gene
Compartment Confidence
cytosol 5
endosome 4
golgi apparatus 2
lysosome 2
nucleus 2
vacuole 2
cytoskeleton 1

Gene Ontology (GO) - Cellular Components for VPS35 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005765 lysosomal membrane IDA 17897319
GO:0005768 endosome IDA --
GO:0005769 early endosome IDA 20164305
GO:0005770 late endosome IBA --
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with VPS35: view

Pathways for VPS35 Gene

genes like me logo Genes that share pathways with VPS35: view

Pathways by source for VPS35 Gene

Gene Ontology (GO) - Biological Process for VPS35 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006886 intracellular protein transport IBA --
GO:0008219 cell death --
GO:0015031 protein transport --
GO:0042147 retrograde transport, endosome to Golgi NAS 11102511
GO:0045056 transcytosis IDA 15247922
genes like me logo Genes that share ontologies with VPS35: view

Transcripts for VPS35 Gene

Unigene Clusters for VPS35 Gene

Vacuolar protein sorting 35 homolog (S. cerevisiae):
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for VPS35 Gene

ExUns: 1a · 1b ^ 2a · 2b ^ 3 ^ 4a · 4b ^ 5a · 5b ^ 6a · 6b ^ 7 ^ 8a · 8b ^ 9a · 9b · 9c · 9d ^ 10a · 10b · 10c · 10d ^ 11 ^ 12 ^ 13 ^ 14 ^
SP1: - - - - -
SP2: - - - -
SP3: - - - - -
SP4: - - - - - - -
SP5: - - - - - - -
SP6: - - - - - - - -
SP7: - - - - - - - - - - - - - -
SP8: - - - - - -
SP9: - - -
SP10: - - -
SP11:
SP12:
SP13:
SP14: - -

ExUns: 15 ^ 16 ^ 17 ^ 18 ^ 19a · 19b ^ 20a · 20b ^ 21
SP1:
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:
SP10:
SP11: -
SP12:
SP13:
SP14:

Relevant External Links for VPS35 Gene

GeneLoc Exon Structure for
VPS35
ECgene alternative splicing isoforms for
VPS35

Expression for VPS35 Gene

mRNA expression in normal human tissues for VPS35 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for VPS35 Gene

SOURCE GeneReport for Unigene cluster for VPS35 Gene Hs.454528

mRNA Expression by UniProt/SwissProt for VPS35 Gene

Q96QK1-VPS35_HUMAN
Tissue specificity: Ubiquitous. Highly expressed in heart, brain, placenta, skeletal muscle, spleen, thymus, testis, ovary, small intestine, kidney and colon
genes like me logo Genes that share expressions with VPS35: view

No data available for mRNA differential expression in normal tissues for VPS35 Gene

Orthologs for VPS35 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for VPS35 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia VPS35 35
  • 99.71 (n)
  • 100 (a)
VPS35 36
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia VPS35 35
  • 94.64 (n)
  • 99.75 (a)
VPS35 36
  • 100 (a)
OneToOne
dog
(Canis familiaris)
Mammalia VPS35 35
  • 94.85 (n)
  • 99.75 (a)
VPS35 36
  • 100 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Vps35 35
  • 91.46 (n)
  • 99.37 (a)
Vps35 16
Vps35 36
  • 99 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia VPS35 36
  • 99 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia -- 36
  • 100 (a)
OneToMany
-- 36
  • 99 (a)
OneToMany
rat
(Rattus norvegicus)
Mammalia Vps35 35
  • 91.54 (n)
  • 99.37 (a)
chicken
(Gallus gallus)
Aves VPS35 35
  • 84.21 (n)
  • 97.99 (a)
VPS35 36
  • 98 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia VPS35 36
  • 92 (a)
OneToOne
African clawed frog
(Xenopus laevis)
Amphibia Xl.8144 35
tropical clawed frog
(Silurana tropicalis)
Amphibia Str.4247 35
zebrafish
(Danio rerio)
Actinopterygii vps35 35
  • 76.76 (n)
  • 93.97 (a)
vps35 36
  • 88 (a)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP007683 35
  • 60.71 (n)
  • 64.88 (a)
fruit fly
(Drosophila melanogaster)
Insecta Vps35 35
  • 60.03 (n)
  • 63.33 (a)
Vps35 36
  • 59 (a)
OneToOne
CG5625 37
  • 58 (a)
worm
(Caenorhabditis elegans)
Secernentea vps-35 35
  • 55.04 (n)
  • 49.94 (a)
vps-35 36
  • 47 (a)
OneToOne
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_AEL107W 35
  • 46.63 (n)
  • 37 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes VPS35 35
  • 52.12 (n)
  • 41.81 (a)
VPS35 36
  • 28 (a)
OneToOne
VPS35 38
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0B07535g 35
  • 47.47 (n)
  • 37.76 (a)
thale cress
(Arabidopsis thaliana)
eudicotyledons VPS35B 35
  • 52.62 (n)
  • 44.88 (a)
rice
(Oryza sativa)
Liliopsida Os03g0801600 35
  • 53.42 (n)
  • 47.45 (a)
bread mold
(Neurospora crassa)
Ascomycetes NCU06284 35
  • 51.16 (n)
  • 47.44 (a)
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes vps35 35
  • 48.53 (n)
  • 38.4 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 65 (a)
OneToOne
Species with no ortholog for VPS35:
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for VPS35 Gene

ENSEMBL:
Gene Tree for VPS35 (if available)
TreeFam:
Gene Tree for VPS35 (if available)

Paralogs for VPS35 Gene

Selected SIMAP similar genes for VPS35 Gene using alignment to 4 proteins:

Pseudogenes.org Pseudogenes for VPS35 Gene

genes like me logo Genes that share paralogs with VPS35: view

No data available for Paralogs for VPS35 Gene

Variants for VPS35 Gene

Sequence variations from dbSNP and Humsavar for VPS35 Gene

SNP ID Clin Chr 16 pos Sequence Context AA Info Type MAF
rs36309 -- 46,671,037(-) GTAGG(C/T)GTATC intron-variant
rs36310 -- 46,671,590(-) TTGCA(A/G)CTGAA intron-variant
rs36312 -- 46,684,812(-) TTATT(C/T)ATCCA intron-variant
rs36313 -- 46,686,207(-) TTCTG(A/G)CACAT intron-variant
rs42907 -- 46,682,524(-) AGGAT(A/T)GTATC intron-variant

Structural Variations from Database of Genomic Variants (DGV) for VPS35 Gene

Variant ID Type Subtype PubMed ID
nsv526656 CNV Gain 19592680
nsv428327 CNV Gain 18775914

Relevant External Links for VPS35 Gene

HapMap Linkage Disequilibrium report
VPS35
Human Gene Mutation Database (HGMD)
VPS35

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for VPS35 Gene

Disorders for VPS35 Gene

(1) OMIM Diseases for VPS35 Gene (601501)

UniProtKB/Swiss-Prot

VPS35_HUMAN
  • Parkinson disease 17 (PARK17) [MIM:614203]: An autosomal dominant, adult-onset form of Parkinson disease. Parkinson disease is a complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. {ECO:0000269 PubMed:21763482, ECO:0000269 PubMed:21763483, ECO:0000269 PubMed:22517097}. Note=The disease is caused by mutations affecting the gene represented in this entry.

(1) University of Copenhagen DISEASES for VPS35 Gene

genes like me logo Genes that share disorders with VPS35: view

Publications for VPS35 Gene

  1. Human homologues of yeast vacuolar protein sorting 29 and 35. (PMID: 11062004) Edgar A.J. … Polak J.M. (Biochem. Biophys. Res. Commun. 2000) 3 4 23
  2. Membrane recruitment of the cargo-selective retromer subcomplex is catalysed by the small GTPase Rab7 and inhibited by the Rab-GAP TBC1D5. (PMID: 19531583) Seaman M.N. … Bright N. (J. Cell. Sci. 2009) 3 4 23
  3. Cloning and characterization of human VPS35 and mouse Vps35 and mapping of VPS35 to human chromosome 16q13-q21. (PMID: 11112353) Zhang P. … Zhao S. (Genomics 2000) 2 3 4
  4. VPS35 mutations in Parkinson disease. (PMID: 21763482) Vilarino-Guell C. … Farrer M.J. (Am. J. Hum. Genet. 2011) 2 3 4
  5. A mutation in VPS35, encoding a subunit of the retromer complex, causes late-onset Parkinson disease. (PMID: 21763483) Zimprich A. … Strom T.M. (Am. J. Hum. Genet. 2011) 3 4

Products for VPS35 Gene

  • Addgene plasmids for VPS35

Sources for VPS35 Gene

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